18 Customer Reviews

Phosphorylation of PPARg in epididymal white adipose tissue in ob/ob mice after treatment with MEK inhibitors. Gene expression in ob/ob epididymal white adipose tissue after treatment with vehicle or either of two MEK inhibitors, PD0325901 or GSK1120212 (n = 7, 7 and 8, respectively). Areas under the curve and gene expression were analysed by analysis of variance.

Nature
2015
517(7534), 391-5.
PD0325901 purchased from Selleck.

Immunoblot analysis of Ser9-phosphorylated (that is, inactivated) or total GSK3β, active or total β-catenin Thr202- and Tyr204- phosphorylated or total Erk1/2, and Ser473-phosphorylated or total Akt in control; Bcl2 lymphoma cells treated with ADR for five days, together with pharmacological inhibitors targeting MAPK and PI3K kinase pathways.α -Tubulin was used as a loading control. MAPKi=PD325901.

Nature, 2018, 553(7686):96-100.
PD0325901 purchased from Selleck.

c, Examples of CDK2 activity traces aligned to the end of mitosis. Each panel shows different time windows relative to mitosis when mitogens were withdrawn (marked in grey) in d. d, Probability of proliferation (defined as CDK2 activity > 1, 10 h after mitosis) represented as a function of time when inhibitors of MEK (MEKi; 100 nM PD0325901) or of CDK4 (CDK4i; 1 μ M palbociclib) were added or when mitogens were removed, relative to mitosis. Data are mean ± s.e.m. (n = 5 biological replicates).

Pharmacological inhibition of MEK (PD0325901) suppresses DR5 expression in cancer cells; this effect is reversible upon stopping of the treatment. The indicated cancer cell lines were exposed to the given concentrations of the inhibitors as indicated for 16 h. TPC-1 cells were treated with 10 uM of the indicated inhibitors for different times as labeled.

Oncogene
2015
10.1038/onc.2015.97.
PD0325901 purchased from Selleck.

(B)Effect of MAPK pathway inhibition on FGF9 mediated induction of Fgf23 expression. (D) Western blot analysis of FRS2 and ERK1/2 phosphorylation in UMR 106 cells. Cells were treated for 3h (Western blot) or 24h (qPCR analysis) with FGF9 (50ng/ml), EGF (50ng/ml), PD173074 (250nM), PD0325901 (100nM) and RAF265 (500nM) as indicated. Heparin (10g/ml) was added to all treatments with FGF9. Activation of Fgf23 is shown relative to transcript levels in vehicle treated cells (relative expression of 1). Expression values were normalized to Gapdh mRNA copies and are given as average with SEM (n3). Data were compared by 1 way ANOVA; asterisk indicates p<0.05 with respect to vehicle treated cells.

Assessment of in vivo toxicity to MEK inhibitor PD0325901. (A) Weight change in grams is shown for each PD0325901 (PD) treatment group in the MDA-MB-453 xenograft model. Weight change is the difference between pre- and post-treatment weight in each group. PD0325901 treatments were carried out at 5, 10, 15 and 20 mg/kg/day for 30 days, and daily gavage of carrier solution was used as control. *P < 0.01 for PD-5/PD-10 vs. control groups and PD-5/PD-10 vs. PD-15/PD-20 groups using Mann-Whitney U test. Error bars: ±2 SEM. (B) Number of days lost due to toxicity is shown for each PD0325901 treatment group in mouse xenograft model explained in Figure 5A. *P < 0.01 for PD-5/PD-10 vs. PD-15/PD-20 groups.

Breast Cancer Res
2011
13, R36.
PD0325901 purchased from Selleck.

The therapeutic effect of AR and MEK inhibitors on in vivo angiogenesis. (A) Angiogenesis index for each in vivo treatment group. Angiogenesis was measured as the number of CD-31-positive blood vessels in a cross-section of each xenograft tumor. CTL: control group; FLU: flutamide; and PD: PD0325901. *P < 0.03 for PD0325901 monotherapy vs. control and **P < 0.03 for combination therapy vs. monotherapy groups using Mann-Whitney U test. Error bars: ±2 SEM. (B) Immunohistochemistry (IHC) was used to measure angiogenesis in a control xenograft tumor. Staining was performed using a CD31 rabbit polyclonal antibody. Original magnification, × 40. (C) IHC was used to measure angiogenesis in a PD0325901 monotherapy tumor. Original magnification, × 40. (D) IHC was used to measure angiogenesis in a xenograft tumor treated with combination therapy. Original magnification, × 40.

Breast Cancer Res
2011
13, R36.
PD0325901 purchased from Selleck.

Effects of the MEK inhibitor (MEKi) PD0325901 (PD) and rhBMP-2 (BMP) treatment on histology in an NF1 open fracture model. Treatment with 10 mg/kg of PD0325901 on days 22 through 10 (PD alone) slightly improved bone volume and callus size. Delivery of 10 mg of rhBMP-2 in the collagen sponge (BMP alone) resulted in a large increase in bone volume and callus size. Combination treatment with local rhBMP-2 and systemic PD0325901 (PD 1 BMP) resulted in further increases in new bone volume and total callus volume.Picro Sirius Red and Alcian Blue staining to assess fibrous tissue.

Effect of small molecule inhibitors on reprogramming efficiency of myoblast cell derived from 5 different donors. (A) Reprogramming efficiency is shown as number of colonies from 10^5 starting cells on Y-axes. Ctrl, control condition and addition of small molecule inhibitors are marked. (B) AP staining of reprogrammed myoblast cell lines,from 5 different donors, in wells of 12-well plates at day 18. Ctrl, control condition and additions of small molecule inhibitors are marked.

The effects of PD0325901 on the Akt/mTOR and MAPK pathways in the two DDLS cell lines as evaluated by western blotting

Tumour Biol, 2016, 37(4):4767-76..
PD0325901 purchased from Selleck.

PD0325901 inhibited the sorafenib-induced RAS/ERK pathway activation and enhanced the cytotoxic effects of sorafenib in resistant cell lines. (A) HUH-7 hepatoma cells treated with sorafenib (5 μM) for 24 h with or without pretreatment with specific kinase inhibitors (PD0325901, 10 μM). Expressions of p-AKT and cleaved PARP were revealed by Western blotting. (B) SK-HEP-1 hepatoma cells treated with sorafenib (5 μM) for 24 h with or without pretreatment with specific kinase inhibitors (PD0325901, 10 μM). Expressions of p-AKT and cleaved PARP were revealed by Western blotting. (C) HUH-7 hepatoma cells treated with sorafenib (5 μM) with or without the kinase inhibitors for 24 h. Proportions of apoptotic cells were evaluated by annexin V labeling. (D) SK-HEP-1 hepatoma cells treated with sorafenib (5 μM) with or without the kinase inhibitors for 24 h. Proportions of apoptotic cells were evaluated by annexin V labeling. (*P<0.05, HUH- 7, SK-HEP-1 are control groups, R-HUH-7, R-SK-HEP-1 are resistant groups).

J Surg Res, 2016, 206(2):371-379.
PD0325901 purchased from Selleck.

Inhibition of anchorage-independent growth of lung tumor cell lines by selected inhibitors. Each selected cell line was treated with the indicated inhibitor at 0.1 μM and 1 μM concentrations for two weeks and cell colony size formation was scored under the Nikon inverted-phase microscope.

PD0325901 shows higher permeability than CI-1040, another MEK inhibitor. PD0325901 should be able to achieve higher systemic exposures than CI-1040. [1] PD0325901 is exquisitely specific and highly potent against purified MEK, revealing a Kiapp of 1 nM against activated MEK1 and MEK2. [2] PD0325901 is roughly 500-fold more potent than CI-1040 with respect to its cellular effects on phosphorylation of ERK1 and ERK2, displaying subnanomolar activity. [2] PD0325901 prevents the growth of melanoma cell lines. PD0325901 inhibits the growth of TPC-1 cells and K2 cells with GI50 of 11 nM and 6.3 nM, respectively. [3] PD0325901 significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM) and only moderately increases the growth of the PTC cells carrying the RET/PTC1 rearrangement at the same concentration. PD0325901 effectively inhibits the phosphorylation of ERK1/2 in multiple PTC cell lines. [3]

The improved potency of PD0325901 relative to CI-1040 is evident. A single oral dose of PD0325901 (25 mg/kg) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. In contrast, CI-1040 at a much higher dose (150 mg/kg) only inhibit pERK levels for roughly 8 hours, returning to control levels by 24 hours after treatment. [2] Therefore, the dose required to produce a 70% incidence of complete tumor responses (C26 model) is 25 mg/kg/day versus 900 mg/kg/day for PD0325901 and CI-1040, respectively. Anticancer activity of PD 0325901 has been demonstrated for a broad spectrum of human tumor xenografts. [2] After 1 week of oral administration of PD0325901 (20–25 mg/kg/day) in mice, no tumor growth is detected in mice inoculated with PTC cells bearing a BRAF mutation. [3] For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor is decreased by 58% as compared with controls. In conclusion, PTC cells carrying a BRAF mutation are more sensitive to PD0325901 than are PTC cells carrying the RET/PTC1 rearrangement. [3]

PTC cells (1 × 104) are seeded in 24-well plates with 1 mL of medium for 4 days in a 37 °C incubator. MEK inhibitor PD0325901 at varying concentrations is added to the cells in triplicate on day 0. MTT dissolved in 0.8% NaCl solution at 5 mg/mL is added to each well (0.2 mL) on day 2 to test GI50 or every day for cell growth curves. The cells are incubated at 37 °C for 3 hours with MTT. The liquid is then aspirated from the wells and discarded. Stained cells are dissolved in 0.5 mL of DMSO and their absorption at 570 nm is measured using a Synergy HT multidetection microplate reader. For GI50, cell growth is calculated as 100 × (T − T0)/(C − T0), where T is the optical density of the wells treated with inhibitors after a 48-hour period, T0 is the optical density at time zero, and C is the control optical density with DMSO only.

Solubility (25°C)

Add solvents to the product individually and in order:
30% PEG 400+5% Tween 80+ddH2OFor best results, use promptly after mixing.

10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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